The major aim of this project is to develop a new integrated MR tracer approach for imaging cerebral blood flow and metabolism in humans, and to apply this approach to study physiological and pharmacological dysfunction in psychiatric patients. The integrated MR tracer approach is similar to 15O PET approaches in that it uses classical tracer theory based on the Kety-Schmidt equation. However, instead of using radioactive tracers, the MR approach uses perturbed magnetic spin states of stable isotopes such as 17O (in 17O2 and H217O) and 1H (in 1H2O) as tracers. Previous work in this project has led to the development and validation of the 17O MR approach for imaging cerebral oxygen consumption, and the development of a technique to image cerebral blood flow, using "spin tagging" of arterial water. In particular, a number of major problems that had precluded the calculation of quantitative cerebral blood flow images in humans have been identified, and theoretical and methodological approaches to overcome these problems have been developed and tested. Using these approaches, the average values for cerebral blood flow in grey and white matter in normal human volunteers were calculated to be 81 + 20 cc/100g/min and 23 + 7 cc/10g/min, respectively. These values agree very well with previous values determined using 15O (PET) approaches. Work in the upcoming two years will focus on the application of MR tracer approaches for imaging regional cerebral blood flow abnormalities in psychiatric patients, under "resting" and "activated" conditions, and on the development of MR tracer approaches for following regional physiological and metabolic changes due to perturbations in specific receptor systems, e.g., the dopamine receptor system.